Endoscopy, in full.

Perform individual gastric risk assessment and staging of precancerous conditions at first-time gastroscopy, irrespective of the patient's country of origin. Use high quality endoscopy with virtual chromoendoscopy (VCE), after proper training, for screening, diagnosis and staging of atrophy and intestinal metaplasia and after endoscopic therapy; VCE guides the biopsy site, with random biopsies taken only when there are no endoscopically suspected changes. Take biopsies from at least two topographic sites, 2 from the antrum/incisura and 2 from the corpus, VCE-guided, in two separate, clearly labeled vials; an additional incisura biopsy is optional, not required. Stage with validated endoscopic classifications of atrophy (e.g. Kimura-Takemoto) or intestinal metaplasia (e.g. EGGIM) to stratify gastric cancer risk (suggestion, weaker than the biopsy recommendation). Follow up patients with extensive endoscopic changes (Kimura C3+ or EGGIM 5+) OR an advanced histological stage that reaches OLGA/OLGIM III/IV, severe atrophy or intestinal metaplasia and/or significant changes in both antrum and corpus rising to stage III/IV, not any intestinal metaplasia or any antrum-plus-corpus involvement on its own, with high quality endoscopy every 3 years, irrespective of country of origin (strong recommendation, moderate quality). Propose NO surveillance for patients with mild to moderate atrophy or intestinal metaplasia restricted to the antrum, in the absence of endoscopic signs of extensive lesions or other risk factors (family history of gastric cancer, incomplete intestinal metaplasia, persistent H. pylori infection), the guideline states this group constitutes most individuals found in clinical practice. Eradicate H. pylori in all patients with precancerous conditions and after endoscopic or surgical therapy. Discontinue or do not start gastric cancer screening or surveillance in asymptomatic individuals over 80, and weigh comorbidities when planning treatment of superficial lesions. Advise smoking cessation; low-dose daily aspirin may be considered for gastric cancer prevention only in selected individuals already at high cardiovascular risk. For visible neoplasia, use ESD for differentiated lesions clinically staged as dysplastic (low or high grade) or intramucosal carcinoma (any size if not ulcerated, or ≤30 mm if ulcerated), with EMR an alternative for Paris 0-IIa lesions ≤10 mm with low likelihood of malignancy. At the population level, endoscopic screening is suggested every 2-3 years in high-risk regions (age-standardized rate >20 per 100,000 person-years), every 5 years in intermediate-risk regions (ASR 10-20) only if cost-effectiveness has been proven, and not at all in low-risk regions (ASR <10).

Distinguish benign from malignant biliary strictures using cross-sectional imaging (MRI/MRCP preferred over contrast-enhanced CT) plus laboratory tests, interpreting CA19-9 after biliary decompression and never relying on tumor markers alone; check serum IgG4 when IgG4-related sclerosing cholangitis is suspected (HISORt criteria). Per the ESGE 2024 diagnostic work-up guideline, tissue-acquisition strategy now branches by stricture location rather than following one linear sequence: for DISTAL extrahepatic strictures with jaundice and no pancreatic mass, combined same-session EUS-guided tissue acquisition (EUS-TA, end-cutting FNB needle) plus ERCP-based tissue acquisition (standard brush cytology plus fluoroscopy-guided biopsy) is the strongly preferred first-line approach; for PERIHILAR strictures, obtain brush cytology plus fluoroscopy-guided biopsy at index ERCP, escalate indeterminate strictures to cholangioscopy-guided biopsy (with intraductal ultrasound/confocal laser endomicroscopy selectively), and reserve EUS-TA for cases where ERCP-based sampling is insufficient and curative resection is not feasible and/or extraluminal disease is accessible; escalate any positive or indeterminate feature to multidisciplinary tumor board. Manage benign anastomotic and chronic-pancreatitis strictures with a fully-covered self-expanding metal stent for 6-12 months (multiple plastic stents when FCSEMS is contraindicated, hepaticojejunostomy if refractory). Treat cholangitis with biliary obstruction as an indication for urgent biliary drainage, but do not instrument every obstructed sector: for hilar or multisegmental strictures (Bismuth II-IV), ESGE suggests draining ≥50% of the liver volume and avoiding opacification of biliary ducts that will not be drained (weak recommendation, low-quality evidence), because post-ERCP cholangitis frequently complicates injection of obstructed ducts that are not subsequently drained, whereas drainage of >50% of liver volume is associated with less cholangitis and longer survival; ESGE suggests antibiotic prophylaxis before biliary stenting in selected patients (e.g., immunocompromised patients, expected incomplete biliary drainage; weak recommendation, moderate-quality evidence), with a full antibiotic course if adequate drainage is not achieved during the procedure. Direct etiology-specific care for Strasberg bile-duct injuries, post-transplant strictures (ASGE 2023: ERCP preferred over PTBD, covered SEMS preferred over multiple plastic stents), IgG4-sclerosing cholangitis, Mirizzi syndrome, and choledochal cysts.

Address the specific underlying cause of persistent or new post-cholecystectomy symptoms after narrowing the heterogeneous differential (retained/CBD stone, sphincter of Oddi dysfunction, bile leak/duct injury, bile acid diarrhea, functional dyspepsia/IBS, GERD). First exclude time-sensitive early postoperative complications, bile leak/duct injury, obstructing retained/CBD stone, biliary obstruction or cholangitis, and treat red-flag features (jaundice, fever, sepsis, or early-onset/worsening pain) as warranting prompt evaluation rather than reassurance; only then reassure that most symptoms settle within 6-12 months, avoid empiric reoperation, and obtain multidisciplinary GI + HPB surgery input for refractory or atypical cases.

For right upper quadrant pain, characterize the pattern (acute vs chronic, post-meal vs unrelated, with vs without fever/jaundice) and triage acute red-flag presentations (Murphy sign, Charcot's triad, painless jaundice with weight loss, pregnancy with LFT/coagulation derangement) to the ED. Obtain labs (CBC, CMP with LFTs, lipase, urinalysis, pregnancy test in reproductive-age women) and RUQ ultrasound as first imaging, then direct further workup by ultrasound findings, cholecystectomy for acute cholecystitis, MRCP for suspected choledocholithiasis based on risk stratification (e.g., high-risk criteria including CBD dilation >6 mm, bilirubin >4 mg/dL, or gallstone pancreatitis), CCK-HIDA/GBEF for acalculous functional gallbladder disorder, and cross-sectional imaging for liver masses or other pathology.

Confirm ulcerative colitis with endoscopy showing continuous colonic inflammation from the rectum plus histology, after excluding infection with two-step CDI testing. Treat mild-moderate disease with 5-ASA by route and extent (suppository for proctitis, enema for left-sided, oral plus rectal for extensive); if 5-ASA fails, treat as moderate-to-severe rather than stepping up gradually. Position advanced therapy by EFFICACY TIER, not by an anti-TNF-first rule. Advanced-therapy-naive, higher efficacy: infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab; intermediate: golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab; lower: adalimumab. PREVIOUSLY TNF-EXPOSED, higher efficacy: tofacitinib, upadacitinib, ustekinumab; lower: adalimumab, vedolizumab, ozanimod, etrasimod - S1P modulators are weakest in exactly this group. Do not cycle within the anti-TNF class after primary non-response; switch mechanism. Apply treat-to-target (STRIDE-II) to endoscopic improvement (MES 0-1). Screen for acute severe UC by Truelove-Witts and admit for IV steroids. Begin CRC surveillance 8-10 years after DIAGNOSIS for extensive or left-sided disease; isolated proctitis follows average-risk screening.

Localized GIST: small (<2 cm) oesophagogastric or duodenal submucosal nodules should be assessed by endoscopic ultrasound and kept under annual surveillance, with excision reserved for lesions that grow or become symptomatic; if a biopsy diagnosis of GIST is obtained, resection is advised unless major morbidity is expected. For all other localized disease, standard treatment is complete surgical excision with microscopically negative (R0) margins, wide margins are not required and routine lymph node dissection is unnecessary because nodal involvement is rare, using function-preserving technique and taking care not to rupture the tumour (rupture worsens prognosis and is treated as metastatic risk). After an R1 (microscopically positive) resection, re-excision may be considered if the original site can be identified and major functional consequences are not expected. Mutational analysis of KIT and PDGFRA is standard practice in all GISTs (it may be omitted only for non-rectal GISTs <2 cm) and guides both prognosis and therapy. Adjuvant imatinib 400 mg/day for 3 years is recommended for completely resected tumours at significant (high) risk of relapse, where risk is estimated from mitotic index, tumour size and tumour site (plus rupture); adjuvant treatment is only appropriate when the mutation is imatinib-sensitive and is not indicated for imatinib-insensitive genotypes such as PDGFRA D842V (and is unlikely to benefit SDH-deficient or NF1-associated GIST). Metastatic or unresectable GIST: first-line imatinib 400 mg/day, except for tumours with a KIT exon 9 mutation where the starting dose is 800 mg/day; treatment is continued indefinitely and should not be interrupted, since interruption is generally followed by progression (surgery of residual/responding metastatic disease may be considered on a case-by-case basis). On progression or intolerance, sequential therapy is second-line sunitinib 50 mg/day (4 weeks on / 2 weeks off, or 37.5 mg/day continuously), third-line regorafenib 160 mg/day (3 weeks on / 1 week off), and fourth-line ripretinib 150 mg/day. PDGFRA D842V-mutant GIST is resistant to imatinib and is treated first-line with avapritinib 300 mg/day (these patients do not receive imatinib).

DIAGNOSIS (patient must be on a gluten-containing diet). Serologic testing consists of TTG-IgA plus, if IgA deficiency has not previously been excluded, concurrent total IgA; if IgA deficiency is present, measure an IgG-based serology (DGP-IgG and/or TTG-IgG). This algorithm, previously restricted to those >=2 years, now applies to adults and children at ANY age. An elevated TTG-IgA should proceed to EGD with duodenal biopsy. A negative TTG-IgA in a non-IgA-deficient patient adequately rules out CD only when pretest probability is low or moderate; in symptomatic patients whose pretest suspicion is high (>5%), EGD with duodenal biopsy should be performed irrespective of serologic result. ACG recommends EGD with multiple duodenal biopsies to confirm the diagnosis in both children and adults with suspicion of CD (STRONG recommendation, moderate quality; 1 dissent); sampling should be 1 or 2 biopsies from the bulb (9-o'clock or 12-o'clock position) and at least 4 from the distal duodenum. Lymphocytic duodenosis (>=25 IELs/100 epithelial cells) without villous atrophy is NOT specific for CD. NONBIOPSY PATHWAY (CONDITIONAL recommendation, moderate quality): a combination of high-level TTG-IgA (>10x ULN) with a positive EMA in a SECOND blood sample is suggested as reliable for diagnosis in CHILDREN, and only if the family agrees with the no-biopsy strategy; in SYMPTOMATIC ADULTS unwilling or unable to undergo upper GI endoscopy the same criteria may be considered AFTER THE FACT, as a diagnosis of 'likely CD', ACG does not endorse a prospective no-biopsy pathway in adults, noting a >=10-fold TTG-IgA elevation carries a PPV of only ~95% in adults, which may be unacceptably low given lifelong treatment implications. HLA-DQ2/DQ8 is not required for diagnosis but is useful for serology-histology discrepancy or in patients already on a GFD; if negative, CD is ruled out. TREATMENT AND MONITORING. Strict lifelong GFD. A visit with a dietitian after diagnosis is MANDATORY, with subsequent visits as needed to reinforce education and adherence encouraged; interview with a dietitian experienced in the GFD is the standard of care for assessing adherence. ACG RECOMMENDS consumption of gluten-free oats (STRONG recommendation, moderate quality), with the qualifier that gluten contamination of oats, variable toxicity across oat varieties, and a small risk of immune reaction to avenin require monitoring for oat tolerance (monitoring intervals are not known). ACG suggests AGAINST routine use of gluten detection devices in food or biospecimens (conditional, low quality; 1 dissent), and finds INSUFFICIENT EVIDENCE to recommend for or against probiotics (evidence gap). ACG suggests setting a goal of intestinal healing as an end point of GFD therapy, advocating individualized discussion of goals beyond clinical and serological remission (CONDITIONAL recommendation, low quality). Follow-up may require multiple visits in the first year (e.g. 3, 6, and 12 months) and regular visits (e.g. twice a year or yearly) thereafter, tracking symptoms and TTG or DGP serology; other tests may include CBC, ALT, AST, vitamins A/D/E/B12, copper, zinc, folic acid, ferritin, and iron, with follow-up bloodwork individualized to verify correction of values abnormal at baseline. Preventive care includes vaccines and DXA. Symptoms improve within days of strict adherence (diarrhea improved in 80% within 60 days), but mucosal healing lags: median time from GFD onset to mucosal healing in adults is 3 years, so it is reasonable to consider a follow-up biopsy in adults after 2 years of starting a GFD, in the ABSENCE of symptoms, after shared decision-making; children heal faster (95% within 2 years), altering the risk-benefit calculus. Repeat biopsy is the only reliable method to document mucosal healing, seroconversion correlates poorly. Upper endoscopy with biopsies is also indicated for lack of clinical response or relapse of symptoms despite a GFD. VACCINATION: ACG suggests vaccination to prevent pneumococcal disease in patients with CD (CONDITIONAL recommendation, low quality), because increased pneumococcal risk is attributed to hyposplenism (frequently subclinical) present in roughly one-third of patients. The regimen follows CDC recommendations by age, immunization record, and comorbidity: for an adult with CD and functional asplenia not previously vaccinated or with unknown history, 1 dose of PCV15 (followed by PPSV23 at least 1 year later) or 1 dose of PCV20 (no PPSV23 indicated); for an adult with CD and no other condition carrying a specific CDC recommendation, ACG suggests 1 dose of PCV20 alone, or 1 dose of PCV15 first and then consider PPSV23 at least 1 year later. NONRESPONSIVE CD (NRCD): defined as persistent symptoms, signs, or laboratory abnormalities typical of CD despite 6-12 MONTHS of dietary gluten avoidance. Evaluation should review and confirm the initial diagnosis of CD, assess for inadvertent gluten exposure (via expert dietitian assessment and serology, positive serologies despite 12 months of GFD suggest ongoing gluten ingestion), assess for a coexisting functional disorder, and selectively test based on clinical suspicion for food intolerances (e.g. lactose, fructose), pancreatic insufficiency, microscopic colitis, and small intestinal bacterial overgrowth, among others. REFRACTORY CD (RCD) is a separate, rarer entity (<1% of patients outside referral centers): ongoing malabsorptive symptoms and signs with villous atrophy despite strict adherence to a GFD for MORE THAN 12 months and absence of other disorders including overt lymphoma; initial assessment centers on distinguishing RCD type 1 from type 2 by CD3/CD8 immunostains, T-cell receptor clonality by PCR, and/or flow cytometry of duodenal biopsies.

For ALL patients undergoing ERCP (average-risk and high-risk alike), give periprocedural rectal NSAID prophylaxis (100 mg indomethacin or diclofenac) unless contraindicated (e.g., recent PUD, renal insufficiency), this is now a strong recommendation for unselected patients, not just high-risk ones. For high-risk patients undergoing repeated or deep pancreatic-duct access or ampullectomy, add a prophylactic small-caliber pancreatic duct stent (3-5Fr, preferably 5Fr, 3-7cm, removed within 5-10 days), strong recommendation; for other high-risk scenarios (difficult cannulation, prior PEP, precut sphincterotomy without fistulotomy), PD stenting is a conditional recommendation when PD access is easily achieved. Aggressive periprocedural/postprocedural IV hydration with lactated Ringer's (20 mL/kg bolus, then 3 mL/kg/h for 8h) is a conditional suggestion for unselected patients (most practical for inpatients), and wire-guided cannulation is conditionally favored over contrast-guided to reduce PEP risk. The SVI trial (Elmunzer, Lancet 2024) found rectal indomethacin alone did NOT meet non-inferiority versus indomethacin+stent in high-risk patients (PEP 14.9% vs 11.3%), supporting continued use of the combination bundle in high-risk cases rather than dropping the stent. Post-procedure, monitor for the major complications (pancreatitis, sphincterotomy bleeding, perforation, cholangitis) and manage by type, PEP by Cotton criteria with fluids/analgesia, bleeding with repeat endoscopic hemostasis, perforation by Stapfer classification with surgical consult for Type I, and cholangitis with empiric antibiotics (Tokyo Guidelines TG18) plus biliary drainage; these complication-management elements are unchanged from ESGE 2020.

DIAGNOSIS: Use fecal calprotectin (cutoff >50-100 μg/g) to differentiate inflammatory from noninflammatory disease OF THE COLON (strong, moderate). Ileocolonoscopy with biopsies for suspected CD; biopsy uninvolved mucosa to define histologic extent; small bowel imaging is part of the initial workup (key concepts, ungraded). CT enterography is comparable to MR enterography for small bowel detection; MRE should be used PREFERENTIALLY in patients younger than 35 years and where serial examinations are likely, because of radiation avoidance, MRE is not a blanket first choice. Intestinal ultrasound is a radiation-free ADJUNCT to diagnosis and to monitoring treatment response (key concept, ungraded, not a graded recommendation). Perform routine endoscopic CRC surveillance in Crohn's colitis (strong, moderate). MILD-TO-MODERATE / LOWER PROGRESSION RISK: Recommend AGAINST oral mesalamine for induction or maintenance (strong, moderate); sulfasalazine should be considered ONLY for symptomatic mild COLONIC CD (key concept). Controlled ileal-release budesonide 9 mg daily for induction of symptomatic remission in mildly-to-moderately active ileocecal CD (strong, moderate), but recommend AGAINST ileal-release budesonide for MAINTENANCE (strong, low). MODERATE-TO-SEVERE / HIGHER RISK: SUGGEST AGAINST requiring failure of conventional therapy before initiating advanced therapy (conditional, LOW, a permission to skip step-up, not a mandate to start advanced therapy upfront). Oral corticosteroids for short-term induction only (strong, low). Recommend AGAINST azathioprine 1.5-2.5 mg/kg/d and 6-mercaptopurine 0.75-1.5 mg/kg/d for INDUCTION (strong, moderate), but SUGGEST the same agents and doses for MAINTENANCE after corticosteroid-induced remission (conditional, low). Check TPMT before starting azathioprine/6-MP (strong, low); measure NUDT15 variants in patients of East Asian ancestry and TPMT variants in all patients prior to thiopurine initiation (strong, moderate). Methotrexate up to 25 mg weekly IM/SC for maintenance after corticosteroid induction (conditional, low). Anti-TNF agents (IV infliximab, SC adalimumab, SC certolizumab pegol) for induction and maintenance (strong, moderate). Recommend COMBINATION IV infliximab + thiopurine over either agent alone in patients naive to both (strong, moderate). Vedolizumab IV for induction and maintenance of symptomatic remission (strong, moderate). Ustekinumab (strong, moderate); risankizumab (strong, moderate), and risankizumab over ustekinumab in prior anti-TNF exposure (conditional, low); mirikizumab (strong, moderate); guselkumab IV-then-SC or all-SC (strong, moderate). Upadacitinib for induction and maintenance in patients PREVIOUSLY EXPOSED TO ANTI-TNF (strong, moderate), the ACG does not endorse it as a first-line biologic-naive option. SC infliximab and SC vedolizumab are maintenance options in responders to IV induction (strong, moderate). PERIANAL FISTULIZING: infliximab for induction (strong, moderate); adalimumab (conditional, low); antibiotics added to infliximab or adalimumab (conditional, very low); vedolizumab, ustekinumab, upadacitinib each (conditional, VERY LOW). Drain perianal abscesses and place setons before escalating advanced therapy (key concept). POST-OPERATIVE: endoscopic assessment at 6-12 months after surgically induced remission over no monitoring (conditional, moderate); in LOW post-op recurrence risk, continued observation rather than immediate medical therapy (conditional, very low); imidazole antibiotics (metronidazole) 1-2 g/d after small intestinal resection (conditional, low); in HIGH-risk CD, anti-TNF to prevent endoscopic recurrence (STRONG, moderate) and vedolizumab (CONDITIONAL, low), these two are not co-equal. SURGERY/ABSCESS: intra-abdominal abscess >2 cm should be treated with antibiotics plus a drainage procedure, and immunosuppression HELD until drainage is achieved (conditional, low). DISEASE MODIFIERS: counsel active smokers to quit; use NSAIDs with caution; assess stress, depression and anxiety as part of comprehensive care (key concepts).